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General Medication Discussion This section is to be used for general medication discussion and other medications not broken out in their own respective forums.

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Old 11-03-08, 01:41 AM
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ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

What are stimulants and how do they work?
**First off, I am not a doctor, so do not take this as medical advise! This informational attempts to go somewhat in depth with this subject of stimulants and how they work, but keeps some of the specific "complicated" details out of it. Let me know if I missed anything. It helps to be able to point people here if they have questions about stimulant medication.**

In order to understand stimulants, we first must understand what things they effect in our brain, namely neurotransmitters.

Neurotransmitters

Neurotransmitters are monoamines, which are chemicals in our brain that modulate(adjust) signals between cells and neurons. The space in between neurons and cells is called the synaptic cleft, and the levels of neurotransmitters in the synaptic cleft affect many effects and feelings. Remember this top part, because this is important.

There are a group of neurotransmitters(called catecholamines) that are chemically similar to Phenethylamine(pictured below). Out of the three, two of them are important neurotransmitters that have shown a positive correlation to ADD/ADHD symptoms and feelings(the other one is associated with depression and mood). These two neurotransmitters are: Dopamine and Norepinephrine.
  • Norepinephrine is a neurotransmitter that increases heart rate, elicits the fight-or-flight response, increases blood flow to skeletal muscles, and slows digestion of food in the stomach (and triggers release of glucose from body stores). It is also associated with (at higher levels): anxiety, physical shakes, and irritablity.
  • Dopamine is a neurotransmitter that has a direct effect on the "reward signaling" in the brain. Behavior, motor activity, cognition, motivation, attention, reward, learning, and mood are effected, but it is not known how dopamine causes this effect. Drugs that increase levels of dopamine are known to have a high risk of addiction. It is hypothesized that dopamine signals reward in the brain, which relates to pleasure, and euphoria when certain levels are reached. Amphtamines, methylphenidate, and cocaine are the most well known drugs that modulate dopamine levels in the brain. High levels of dopamine naturally is associated with schizophrenia. High levels of dopamine due to drug use is typically associated with psychosis, or in short abnormal thoughts and actions. Drug induced psychosis can be reversed with ceased use of the drug.


Chemical Phenethylamine, a chemical similar to amphetamines, methylphenidate and neurotransmitters.


Stimulant medication categories

Essentially there are two different stimulant based medications to treat add/adhd; methylphenidate (Ritalin, Rilatine, Attenta, and Methylin, Concerta, Metadate CD, Methylin ER, Ritalin LA, and Ritalin-SR), and amphetamines (adderall, dexedrine, dextrostat, desoxyn). These both act as NDRIs (Norepinephrine and Dopamine Reuptake Inhibitors), but amphetamines also stimulate Norepinephrine and Dopamine vesicle releases.

------------------------------------------------------------------------

Methylphenidate

Ritalin, or Methylphenidate is a CNS stimulant used to treat ADHD and narcolepsy. It has a binding affinity(high attraction) for both the norepinephrine transporter, and the dopamine transporter. When it binds to these transporters, it prevents these transporters from taking away the two neurotransmitters in the synaptic cleft(remember the first paragraph?), which creates an elevated level of both dopamine and norepinephrine, leading to effects as stated above. In pharmacology, it is simply called a dopamine and norepinephrine reuptake inhibitor (prevents(inhibits) the transporters from taking away(reuptake) dopamine and norepinephrine.


Methylphenidate, or more common: ritalin

Quote:
*Contrary to popular myths perpetuated by fear mongers on the internet and worldwide, methylphenidate (ritalin) is NOT amphetamine, NOR is it cocaine. These drugs have somewhat similar effects, but are NOT chemically similar. A similar comparison would be like comparing hydrocodone (vicodin) to heroin. Both have similar actions and are in the same class of drugs, but the extent of effects and their chemical makeup is different.
------------------------------------------------------------------------

Amphetamine

Amphetamine is a CNS stimulant used to treat ADHD and narcolepsy. It affects norepinephrine, dopamine, and (to a lesser extent) serotonin. It binds to norepinephrine and dopamine transporters (inhibiting them), along with stimulating and promoting the release of dopamine and norepinephrine neurotransmitters (and again in some areas of the brain, a minor effect on serotonin) into the synaptic cleft. Pharmacologically speaking, amphetamine is a dopamine, norepinephrine (and minorly serotonin) releaser and reuptake inhibitor.

Racemic amphetamine, or alpha-methylphenethylamine

Different amphetamine "types" are used for treatment. These three are the most popular:

------------------------------------------------------------------------

Adderall (mixed amphetamine salts)
Adderall is a trademarked name held by Shire that is a mixture of 4 amphetamine salts.
  • 1/4 dextroamphetamine sulfate
  • 1/4 dextroamphetamine saccharate
  • 1/4 (racemic d/l-amphetamine) sulfate
  • 1/4 (racemic d/l-amphetamine) aspartate monohydrate
So adderall is 75% dextro-amphetamine (in the sulfate, saccharate, and aspartate monohydrate salts), and 25% levo-amphetamine(in the sulfate and aspartate monohydrate salts). These different salts are said to have different digestion and blood level rates, which allow a more stable level of neurotransmitter modulators instead of a bell shaped curve.

Dextro-amphetamine and levo-amphetamine(d- and l- amphetamine) are known for these summarized and generalized differences.
D-Amphetamine
  • Very strong CNS (brain) stimulation, and a low PNS (body) stimulation.
  • Has a higher affinity for increasing dopamine levels vs. norepinephrine.
  • Typically less physical side effects than l-amphetamine.
  • Shorter half-life (effects are shorter) than L-amphetamine.
  • Longer onset time (takes longer to kick in) than L-amphetamine.
L-Amphetamine
  • Strong PNS (body) stimulation, and a to a lesser effect, medium to low CNS (brain) stimulation.
  • Has a higher affinity for increasing norepinephrine levels vs. dopamine.
  • Typically more physical side effects than D-amphetamine.
  • Longer half-life (effects last longer) than D-amphetamine.
  • Shorter onset time (kicks in quicker) than L-amphetamine.

------------------------------------------------------------------------

Dextostat (D-amphetamine sulfate)
Usually associated with less side effects than adderall, with a greater ability of concentration.
  • Very strong CNS (brain) stimulation, and a low PNS (body) stimulation.
  • Has a higher affinity for increasing dopamine levels vs. norepinephrine.
  • Typically less physical side effects than l-amphetamine.
  • Shorter half-life (effects are shorter) than L-amphetamine.
  • Longer onset time (takes longer to kick in) than L-amphetamine.

D-amphetamine, or dextro-amphetamine

------------------------------------------------------------------------

Desoxyn (D-methamphetamine)
This is the strongest drug of the amphetamines in the use of treating add/adhd. It has a methyl group, making it more fat soluble and higher ability to cross the blood brain barrier, which simply put makes it stronger. It has all the similar effects as D-amphetamine, except with the added methyl group, makes the effects stronger and more pronounced.

D-methamphetamine, or methylamphetamine

------------------------------------------------------------------------

Summary

So in short, methylphenidate acts as a stimulant by blocking the transporter from taking certain neruotransmitters out of the synaptic cleft. This leads to higher numbers of these neurotransmitters, and usually leads to typical stimulant feelings when taken by those who have add/adhd: improved concentration, improved impulse control, decreased anxiety, decreased sensory over-stimulation, and decreased fatigue.

And in short here, Amphetamine acts as a stimulant by both blocking the transporters of certain neruotransmitters, along with stimulating release of these neurotransmitters, with MAOI effects. The effect usually lasts longer than methylphenidate, and typically more pronounced.

Stimulants (when used as directed by a qualified doctor/psychiatrist) typically have a very low level of addiction risk, along with low levels of side effects.
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Old 11-03-08, 01:44 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Wow, thanks.
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Old 11-03-08, 06:08 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

- that D- and L- both have bio-activity and that it so differs for chimaers is real interesting -
- pointing towards the idea that we are chimaers also

D-Amp
strong central, weak peripheral

L-Amp
weak central, strong peripheral

Mind : Body duality is often quoted in context of man
- model upon which we may build to understand our context as seemingly 'solid' energetic structures with the capacity to think about

why we're not very happy ?
what we'll have for dinner ?
and why it's not sunny today ?

how advanced are we ?

not
very
it
seems
to
me

- however that doesn't mean that we can't have fun -

- being perfectly ordinary instantiations of natural process doesn't mean that we should drown our ensuing sorrows in
lake -

- has knowledge of the chemical structure of theobromine



ever prevented anybody from enjoying chocolate ?



have memories of the sickly sweet warmth of baby poo on your leg



ever dampened ardour
of young love ?


mind:body duality can be explained with application of chimaerism

central : peripheral
CNS ....: PNS

a chimaeric structure to man (with mind)
as the basis to
mind:body duality.
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Old 11-03-08, 06:11 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

chocolate anybody ?

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Old 11-03-08, 06:05 PM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Thanks for the responses and thank you's. I myself was once clueless when it came to the type of stimulants.

After days/weeks/months of reading and conceptualizing about it, I figured i'd at least TRY to simplify it to people who do not have the same interest in pharmacology that I do .

If anyone has any questions about any of the topics discussed in the first post, feel free to post them here and I will answer them to the best of my ability, or find out.

And to a mod, is there any possibility of getting this stickied? And is there any way to allow editing of it? I had a typo or 2.
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Old 11-03-08, 08:11 PM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

I think this is great. It helped my understanding, certainly.

Where did this info come from? I'd like to see something like this for all of the pharmaceuticals - even the ones that aren't stimulants. Actually, even things like the Omega's would be great to have in a format like this. And I realize some things work but no one knows why.

I know that people who work in this field already know this stuff. But for the majority of people on here this is a bit of a puzzle. I've spent many nights going reading technical postings with another screen open to Google a term I never heard of. We're all trying to solve a puzzle that is our lives, so any hints or clues in putting this all together are really helpful.
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---! I need to update this. I'll put that on the list


No, I don't proofread my postings. I type, I click submit. Then cringe if I go back & read it later.
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Old 11-03-08, 08:21 PM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Don't overlook the effects these drugs have on serotonin. For example, the release of serotonin participates in the overall effect of methamphetamine.

Methylphenidate does not really behave like amphetamine, however it's action is virtually identical to cocaine, the only difference being that methylphenidate is more potent (as well as the obvious differences in pharmacokinetics).

Don't forget the oxazolines, like pemoline (yes, it is no longer used in the US). They are arguably more centrally acting than even methamphetamine, and have less noradrenergic activity. This class, especially the various ring substituted variations, are potent releasers of serotonin, which is not particularly desirable.

Below is pemoline.

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Old 11-03-08, 10:42 PM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Ecu20,
Thanks for the information. I had some understanding of the information you presented but you did a great job of organizing and concisely explaining the different stimulants and how they work. If I might ask, do you work in the medical field or in pharmacology?

My sister is a pharmacist and I've learned some things from her and I also read a lot. Not that I absorb all that I read but I have a much better understanding of the terminology and some basics on how some of the meds work. I just finished reading a textbook on Psychopharmacology that was over 1000 pages. I learned a lot, even if I didn't comprehend everything in the book. And it had lots of illustrations!! I even taught my sister a few things! The saying that "the more you learn, the more you realize you don't know" is so true.
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Old 11-03-08, 11:09 PM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Focalin and the d and l-isomers of methylphenidate should be included in the discussion
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Old 11-04-08, 12:49 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

syou mean you all didnt know this before this post which is like grade 1 stuff.
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Old 11-04-08, 08:53 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

good post.

L-amphetamine actually gives no preference to dopamine or norephinephrine sites. Its activity can vary on a day to day basis in what site(s) it works on.

I also second the idea of including d,l-methlyphenidate in the post. dexmethylphenidate (Focalin) is an entirely different beast than Ritalin.

J
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Old 11-05-08, 03:12 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Quote:
Originally Posted by JR1973 View Post
I also second the idea of including d,l-methlyphenidate in the post. dexmethylphenidate (Focalin) is an entirely different beast than Ritalin.

J
Crosses the blood-brain barrier easier than Ritalin..? different in what way, etc
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Old 11-05-08, 10:52 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Although the theory of Focalin is that you get the benefit of Ritalin at half the dosage (since l-methylphenidate only contributes to peripheral side effects and zero mental benefits) I've found that Focalin is entirely different altogether.
Taking 15mg of Focalin XR is simply not that same as taking 30mg of Ritalin LA (or even 40mg). To me, Focalin seems to 'kick' so much harder than regular Ritalin. I can't really explain it but I believe others here in the forum have experienced similar results from Focalin compared to regular Ritalin.

J
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Old 11-07-08, 12:29 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

Hey thanks! I've been trying to learn about how the meds work for a little while, but I was reading these in depth studies and scientific articles, and they are haard enough to read... ADD just makes them even mroe boring.

But I have a question:
How do the medications affect the hypothalamus? I know that this part of the brain is, to quote my text book,: "involved in a different kind of motivation, including regulation of thirst, sexual behavior, sleep, intensity of emotional reactions, and hunger." I've had problems, and heard from others too, with some of these things when on the medication. I'm just trying to fit the pieces of the puzzle together, I'm just linking those things together, I don't actually know if the hypothalamus is involved in that at all...
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Old 11-08-08, 01:34 AM
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Re: ADD/ADHD FAQ: Want to know what stimulants are, and how do they work? Read this!

I have come to believe that L-amp's effect on the PNS triggers Beta-2 stimulation. Which is the underlying reason L-amp has a stronger profile for norepinephrine.

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